Environmental determinants of IVF treatment

Air pollution and other environmental characteristics are associated with reproductive outcomes and have been shown to increase the risks of preterm birth and low birthweight as well as in utero fetal growth. Very recent evidence has also suggested that exposure to ultraviolet radiation (UVR) during first trimester may be protective against the risks of these birth outcomes. However, although the period around the time of conception (periconception) and embryo implantation are critical for successful and healthy pregnancy very few studies have examined whether air pollution affects conception and none have examined possible associations with UVR exposure despite plausible pathways connecting both exposures. The biggest challenge is the practical problem of accurately identifying the periconception period. One approach that can overcome this is to utilise data on infertility treatments such as In Vitro Fertilisation (IVF) where exact dates of the various stages of an IVF treatment cycle including date of occyte retrieval, embryo transfer and of course date of delivery (where treatment has been successful) are known. A register of all assisted reproduction treatment cycles carried out by fertility clinics in the UK since 1991 to the present day is maintained by the UK Human Fertilisation and Embryology Authority (HFEA) and represents the largest such national register in the world. This study proposes to make novel and unique linkages between the HFEA register and temperature, air pollution and UVR exposure data to examine the association of air pollution and UVR with IVF treatment outcomes. This linkage will be based on the individual's postcode of residence and fertility clinic location. For the subset of Scottish individuals in the register with a recorded birth, we will also link to information recorded at delivery which is contained in the Scottish Morbidity Record 02 which includes more detailed contextual information about the mother. We will examine two outcomes; the odds of successful embryo implantation and the odds of live birth. The project will utilise existing air pollution data that was developed by a member of the current project team in a previous study and will generate and produce estimates of UVR exposure from satellite based irradiance data.

The project has significant potential impacts. Infertility and its associated treatment is a traumatic experience with adverse effects for wider health outcomes as well as associations with family/relationship breakdown and financial problems. The results from this study will improve our understanding of potentially modifiable risk factors for failed infertility treatment and will inform potential policy recommendations relating to managing environmental exposures for individuals undergoing fertility treatment. The HFEA, as a stakeholder in the research are interested and supportive of the project and findings from the project will be presented to them at a dissemination event with an audience including lay members, patient representatives and the general public. As part of the project we will develop a number of new resources including a new dataset of UVR exposure that will be available for other population based studies and the establishment of a new and novel linkage between ART treatment register data and environmental exposure data that will assist future projects. In the future, we envisage that the results will be used as a basis for more costly experimental research to investigate more fully possible mechanisms and pathways that may underlie any observed associations.

Keywords: IVF treatment; Ambient air pollution; UV radiation; Data linkage

The proposed research will produce results of interest to a number of relevant stakeholders. Firstly, the scientific community in the UK will benefit the establishment of the approach and feasibility of linking the HFEA register to spatio-temporal environment data and will provide a novel linkage which could be utilised in future work. The findings will advance our understanding of the effects of UVR and air pollution exposure for IVF treatment success and therefore strengthen the existing evidence base. The project will also develop and generate a UVR exposure dataset based on satellite derived irradiance data. The resulting dataset and the techniques used to create it will be wider of interest to other studies interested in population based UVR exposure. Researchers involved with the project will benefit from the pooled expertise that the project brings together and the potential for spinoff projects that emerge from this new collaboration as the project progresses. In particular, it is envisaged that the results from this relatively low cost linkage study could provide impetus for larger and more costly studies which focus on identifying mechanistic pathways of both UVR and air pollution.

The proposed research will also have impact for regulatory and policy bodies in Scotland and the rest of the UK. The Human Fertilisation and Embryology Authority (HFEA) who hold and supply the register on which the study is based have expressed interest in the research. Their role is to licence UK fertility clinics and to monitor research as well as to provide impartial and authoritative information to the public. The HFEA have indicated interest and support for the project and would request a lay summary document to be published on their website together with links to any academic outputs that are produced. They would also be keen to host a dissemination event to be held in London to be attended by both members of the HFEA which would include lay members and patient representatives and the general public. A letter outlining the support of the HFEA and their contribution towards this event is attached. The research would also be of clear interest to the Infertility Network UK, a patient advocacy group who work closely with the HFEA and we would look to disseminate a short summary of the project of the project findings to them.

This project is an ideal exemplar to continue the crucial work the of the Farr Institute in engaging the public in health informatics research. Tom Clemens, who is a research fellow with the Farr Institute, in Scotland and Longitudinal Studies Centre Scotland, has, in collaboration with the Farr Institute and the Longitudinal Studies Centre Scotland previously designed and delivered public engagement events with the aim of informing the public about how we use and link their data for research purposes and illustrating the benefits of the resulting research. The project will work closely with the public engagement team at the Farr Institute to produce and deliver a similar event using the results from this work as an exemplar.

A number of formal academic outputs will also be produced. The novel linkages involved in the project, the international significance and uniqueness of the HFEA register and the relative sparseness of existing evidence point towards perhaps 2-3 publication in international medical and environmental health journals. As well as this, results will be presented at a national scientific conference such as the international society for environmental epidemiology, the British Fertility Society annual conference or the International Population Data Linkage conference.